Perturbation of cellular signaling cascades modulated by ionizing radiation and environmental stress

Cellular signaling plays a central role in the regulation of several cell functions, which can be perturbed by different external stimuli, including environmental stress and ionizing radiation. The dysregulation of intra- and extracellular mechanisms may alter the correct behaviour of cells. The aim of this work was to investigate the activation of strongly interlaced intracellular signaling pathways, following the exposure to low- and medium-doses of X-rays, with a focus on the mechanisms involved in the inflammatory- and apoptotic-related responses. In particular, the temporal dynamics of the ERK1/2 and PKB/AKT pathways and their possible dose dependences were investigated. The presented results indicate a clear dose dependence of such pathways only at early time points, suggesting a fast response of the system to X-rays and the need for further studies at shorter times after exposures

The role of GP’s compensation schemes in diabetes care: evidence from panel data

The design of incentive schemes that improve quality of care is a central issue for the healthcare sector. Nowadays we observe many pay-for-performance programs, where payment is contingent on meeting indicators of provider effort, but also other alternative strategies have been introduced, for example programs rewarding physicians for participation in diseases management plans. Although it has been recognised that incentive-based remuneration schemes can have an impact on GP behaviour, there is still weak empirical evidence on the extent to which such programs influence health outcomes. We investigate the impact of financial incentives in Regional and Local Health Authority contracts for primary care in the Italian Region Emilia Romagna for the years 2003-05. We focus on avoidable hospitalisations (Ambulatory Care Sensitive Conditions) for patients affected by type 2 diabetes mellitus, for which the assumption of responsibility and the adoption of clinical guidelines are specifically rewarded. We estimate a panel count data model using a Negative Binomial distribution to test the hypothesis that, other things equal, patients under the responsibility of GPs receiving a higher share of their income through these programs are less likely to experience avoidable hospitalisations. Our findings support the hypothesis that financial transfers may contribute to improve quality of care, even when they are not based on the ex-post verification of performances.

Rheumatoid factor: a novel determiner in cancer history

The possible interplay between autoimmunity and cancer is a topic that still needs to be deeply explored. Rheumatoid factors are autoantibodies that are able to bind the constant regions (Fc) of immunoglobulins class G (IgGs). In physiological conditions, their production is a transient event aimed at contributing to the elimination of pathogens as well as limiting a redundant immune response by facilitating the clearance of antibodies and immune complexes. Their production can become persistent in case of different chronic infections or diseases, being for instance a fundamental marker for the diagnosis and prognosis of rheumatoid arthritis. Their presence is also associated with aging. Some studies highlighted how elevated levels of rheumatoid factors (RFs) in the blood of patients are correlated with an increased cancer risk, tumor recurrence, and load and with a reduced response to anti-tumor immunotherapies. In line with their physiological roles, RFs showed in different works the ability to impair in vitro anti-cancer immune responses and effector functions, suggesting their potential immunosuppressive activity in the context of tumor immunity. Thus, the aim of this review is to investigate the emerging role of RFs as determiners of cancer faith

CD137+ T-cells: protagonists of the immunotherapy revolution

The CD137 receptor is expressed by activated antigen-specific T-cells. CD137+ T-cells were identified inside TILs and PBMCs of different tumor types and have proven to be the naturally occurring antitumor effector cells, capable of expressing a wide variability in terms of TCR specificity against both shared and neoantigenic tumor-derived peptides. The aim of this review is thus summarizing and highlighting their role as drivers of patients’ immune responses in anticancer therapies as well as their potential role in future and current strategies of immunotherapy. The CD137 receptor (4-1BB, TNF RSF9) is an activation induced molecule expressed by antigen-specific T-cells. The engagement with its ligand, CD137L, is capable of increasing Tcell survival, proliferation, and cytokine production. This allowed to identify the CD137+ T-cells as the real tumor-specific activated T-cell population. In fact, these cells express various TCRs that are specific for a wide range of tumor-derived peptides, both shared and neoantigenic ones. Moreover, their prevalence in sites close to the tumor and their unicity in killing cancer cells both in vitro and in vivo, raised particular interest in studying their potential role in different strategies of immunotherapy. They indeed showed to be a reliable marker able to predict patient’s outcome to immune-based therapies as well as monitor their response. In addition, the possibility of isolating and expanding this population, turned promising in order to generate effector antitumor T-cells in the context of adoptive T-cell therapies. CD137-targeting monoclonal antibodies have already shown their antitumor efficacy in cancer patients and a number of clinical trials are thus ongoing to test their possible introduction in different combination approaches of immunotherapy. Finally, the intracellular domain of the CD137 receptor was introduced in the anti-CD19 CAR-T cells that were approved by FDA for the treatment of pediatric B-cell leukemia and refractory B-cell lymphoma